Skin antiseptic composition dispenser and methods of use

ABSTRACT

Skin antiseptic composition dispensers and methods of use are disclosed. The skin antiseptic composition dispenser may include a container with one or more walls that are substantially impermeable to ethylene oxide gas during normal ethylene oxide sterilization processes. In some embodiments, the container may include flexible walls free of metallic foil barrier layers. The containers may also include one or more vents in addition to one or more openings used to dispense the skin antiseptic composition within the container. The dispenser may include an applicator with a hydrophilic foam.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. Ser. No. 10/263,518, filed Oct.3, 2002, now allowed, the disclosure of which is incorporated byreference in its entirety herein.

FIELD OF THE INVENTION

The present invention relates to the field of skin antisepticcomposition dispensers.

BACKGROUND

Antiseptic preparation of patient's skin for surgery conventionallyincludes a 3-10 minute scrubbing of the affected area with an antisepticsoap solution followed by the application of a water-soluble antisepticpaint solution.

These solutions are generally applied with saturated sponges that areattached to a blade or held with forceps. These sponges are oftensaturated by soaking them in open pans of solution. Sometimes, spongeswith attached handles are provided in a plastic or aluminum foillaminate pouch containing enough liquid to saturate the sponges. In someproducts the sponges are supplied dry in a sterile “kit” with theantiseptic solutions provided in relatively thin walled 4 oz.polyethylene bottles. These bottles generally have wall thickness lessthan about 500 microns.

While inexpensive, these techniques are messy and offer little controlover inadvertent dripping of the solution into areas where it isundesired. Since many of the available solutions contain activeingredients such as alcohol and iodine which can be irritating ifallowed to pool in areas and left in contact with the skin, good controlover the application has long been desirable.

Over the years, devices have been developed in an attempt to preventsolution dripping associated with these techniques, and to reduce thetime required for application of the antiseptic solution. In particular,the DURAPREP products commercially available from 3M Company (St. Paul,Minn.) have enjoyed commercial success by providing substantiallydrip-free, convenient application of antiseptic solutions.

Coassigned U.S. Pat. No. 4,925,327 describes a liquid applicator thatincorporates a rigid, porous metering insert to regulate the flow rateof liquid between the applicator handle and a foam sponge covering amajor orifice of the handle. The liquid to be dispensed is contained ina rupturable reservoir removably affixed at the other major orifice ofthe handle.

Coassigned U.S. Pat. No. 5,658,084 further discloses a liquid applicatorwhere the liquid is contained in a frangible ampoule inside the body ofthe applicator. This ampoule is supported and protected by a deformableelement that prevents unintentional breakage of the ampoule from impactduring storage and handling before use. The applicator is actuated bypushing at least a portion of the frangible ampoule through an aperturein the deformable element and into contact with a means for breaking theampoule.

One consideration in the design of these delivery devices is to preventcontact between the clinician and the skin of the patient to avoidcontamination. This may be accomplished by providing a handle that ispreferably at least four inches long and oriented at an angle of 30-90degrees to the head of the sponge. While this is convenient forapplication to skin, it is completely unsuitable for applying anantiseptic solution into, e.g., the vaginal canal. In contrast, typicalsponge sticks available in kits have the sponge and handle in the sameplane. While this is suitable for prepping the vaginal canal, it isdifficult to use on skin because of a high potential for contact betweenthe clinician's hand and the patient.

U.S. Pat. No. 4,507,111 illustrates still another surgical scrubdispensing system. In this invention the antiseptic prep solution ishoused in a separate elongated cartridge adapted to be longitudinallyslidable in an elongated hollow handle member. The handle member hasattached thereto an absorbent sponge. The handle member further includestwo hollow spikes formed on the inside of said member which provide flowcommunication from the interior of the hollow handle member to theabsorbent sponge. When the spikes puncture the elongated handle one ofthe spikes serves to vent the container and one of the spikes serves todeliver the fluid. Since both spikes reside on one end of the containerthey must be spaced and the handle held at a precise angle to ensure afluid head difference necessary for proper venting. Many clinicians havebeen trained to hold the applicators in a vertical orientation whenactivating. This applicator would not, however, properly vent when heldvertically.

Typical antiseptic composition applicators are provided with sterileexterior surfaces to avoid contaminating the patient with microorganismsthat could be located on the exterior surfaces of the applicators. Manyof these applicators are sterilized by exposure to ethylene oxide gas.Surprisingly, we have found that kits containing iodophor-basedantiseptic compositions in polyethylene bottles having wall thicknessesof less than about 500 microns contain significant levels of iodohydrin(2-iodoethanol). Iodohydrin is considered quite toxic and is believed tobe formed by reaction of ethylene oxide which has penetrated through thecontainer with hydrogen iodide found in the antiseptic composition.Ethylene oxide itself is also quite toxic and its by product levels inmedical devices are tightly controlled by the Food and DrugAdministration. Similar problems may result from sterilization by othersgases such as hydrogen peroxide plasma and the like. Therefore, even innon-iodophor containing antiseptic compositions, it is highly desirableto prevent ethylene oxide and other chemical sterilants from diffusinginto the container during sterilization.

U.S. Pat. No. 4,799,815 describes a liquid dispensing swab applicatorsystem in which a hermetically sealed fluid filled tube having anabsorbent swab at one end is opened by puncturing the tube with anexternal jig. The fluid flows out over the exterior surface of the tubeand into the swab. This delivery method may not, however, be practicalfor larger fluid volumes of low viscosity fluids that need to bedelivered rapidly (such as presurgical fluids) because the fluid exitsat a rate much faster than the absorbent could absorb the fluidresulting in excessive dripping and mess.

While these products have provided a considerable advance, they arecomplex to manufacture, placing them beyond the means of some healthcare consumers.

SUMMARY OF THE INVENTION

The present invention provides skin antiseptic composition dispensersand methods of use that, in various embodiments, may provide a varietyof advantages.

In some embodiments, the skin antiseptic composition dispenser mayinclude a container with one or more walls that are substantiallyimpermeable to ethylene oxide gas during normal ethylene oxidesterilization processes. Reactive sterilants such as ethylene oxide mayreact with the active antimicrobial agent or with other components inthe skin antiseptic composition altering the potency or producingpotentially toxic compounds. For example, iodine, as well as otherantimicrobial agents, potentially react with ethylene oxide that passesinto the container during sterilization of the exterior surfaces of thedispensers. The effectiveness of such skin antiseptic compositions maybe compromised by exposure to ethylene oxide gas.

In some embodiments, it may be desirable to provide a container thatincludes flexible walls free of metallic foil barrier layers. Apotential advantage of using containers free of metallic foil barrierlayers is that if a metallic foil layer such as, e.g., aluminum foil, isexposed to a skin antiseptic composition containing iodine (e.g., aniodophor composition), the amount of iodine in the antisepticcomposition may be rapidly reduced. Exposure of the antisepticcomposition to metallic foil layers may be through, e.g., pinholes, orother defects in a coating that is otherwise meant to prevent directcontact between the antiseptic composition and the metallic foil layer.Reduction of the iodine levels in the antiseptic composition may beassociated with a reduction in the antiseptic efficacy of thecomposition.

Another potential advantage of containers made with walls that are freeof metallic foil barrier layers is that the walls may preferably betranslucent or transparent. Walls that are translucent or transparentmay allow for visual monitoring of the skin antiseptic compositionwithin the container. In contrast, walls that include metallic foilbarrier layers are typically opaque, thus preventing visual monitoringof the contents of the container.

A further potential advantage of containers made with walls that arefree of metallic foil barrier layers is that the containers may be, insome instances, easily and inexpensively extruded. Extruded tubularcontainers can be produced free of, e.g., fin seals, that may be proneto leakage.

The skin antiseptic composition dispensers may also include one or morevents in addition to one or more openings used to dispense the skinantiseptic composition within the container. The vents may assist indispensing of the skin antiseptic composition from the container to theapplicator. The vents are preferably sealed and the skin antisepticcomposition dispenser may include structures to assist in opening of theseal by twisting or other simple motions. In some instances, the ventseal may be opened by peeling.

In some embodiments, the skin antiseptic composition dispenser includesan applicator with a hydrophilic foam that may be helpful in reducing orpreventing dripping of the skin antiseptic composition from theapplicator during use. Surprisingly, hydrophilic foams have also beenshown to provide superior antimicrobial efficacy as compared toconventional hydrophobic foam pads (when used with aqueous skinantiseptic compositions). The hydrophilic foam may, e.g., have anapparent surface energy of 35 dynes/centimeter or more. Even higherapparent surface energy may be desirable in connection with some skinantiseptic compositions, e.g., apparent surface energy of 40dynes/centimeter or more may be preferred. It may, however, be preferredthat the hydrophilic foams used as applicators in the present inventionhave an apparent surface energy of 45 dynes/centimeter or more, possibly50 dynes/centimeter or more. In some instances, it may be preferred thatthe hydrophilic foam be wettable by deionized water (thus having, e.g.,an apparent surface energy of 70 dynes/centimeter or more).

In some embodiments, the applicator may include a canted major surfacethat forms an angle with a longitudinal axis of the handle (e.g., thecontainer) of the dispenser. The canted major surface may provide forclearance between the hand of the user and the patient's skin to reducethe likelihood of or prevent contact between the user's hand and thepatient's skin during application of the skin antiseptic composition. Ifthe angle formed by the canted major surface is not too large, the skinantiseptic dispenser may be used to apply skin antiseptic composition tothe skin as well as within body orifices, e.g., vagina, rectum, etc.

In one aspect, the present invention provides a skin antisepticcomposition dispenser including a container defining an interior volume;skin antiseptic composition located within the interior volume of thecontainer; a spout attached to the container, wherein the spout has atleast one opening therein; a dispensing seal located between theinterior volume of the container and the spout; and a foam pad locatedover the spout, wherein the foam pad includes hydrophilic foam with anapparent surface energy of 35 dynes per centimeter or more.

In another aspect, the present invention comprises a skin antisepticcomposition dispenser including a container defining an interior volume,wherein the container has a tubular shape that comprises one or moreflexible walls free of metallic foil layers; skin antiseptic compositionlocated within the interior volume of the container; and dispensingmeans for dispensing the skin antiseptic composition. The container isimpermeable to liquid and vapor phases of the skin antisepticcomposition and the container exhibits permeability to gaseous ethyleneoxide of 20 mg/hr/cm² or less.

In another aspect, the present invention provides a skin antisepticcomposition dispenser including a container defining an interior volume,wherein the container includes a tubular shape with one or more flexiblewalls free of metallic foil layers; skin antiseptic composition locatedwithin the interior volume of the container; and dispensing means fordispensing the skin antiseptic composition. The container is impermeableto liquid and vapor phases of the skin antiseptic composition; and theone or more flexible walls free of metallic foil layers include an innerlayer and an outer layer, wherein at least one of the inner layer andthe outer layer is substantially impermeable to ethylene oxide.

In another aspect, the present invention provides a skin antisepticcomposition dispenser including a container defining an interior volume,wherein the container has a first end distal from a second end along alongitudinal axis; skin antiseptic composition located within theinterior volume of the container; at least one dispensing openingproximate the first end of the container; a dispensing seal closing theat least one dispensing opening; at least one vent orifice proximate thesecond end of the container; a vent seal closing the at least one ventorifice; and an applicator attached to the first end of the container,wherein the at least one dispensing opening is in fluid communicationwith the applicator when the dispensing seal is opened. The skinantiseptic composition enters the applicator through the dispensingopening under the force of gravity when the dispensing seal and the ventseal are opened and the at least one vent orifice is located above theat least one dispensing opening.

In another aspect, the present invention provides a method of preparinga skin antiseptic composition dispenser for use by: providing a skinantiseptic composition dispenser as described in the precedingparagraph; opening the dispensing seal, wherein the at least onedispensing opening is in fluid communication with the applicator;opening the vent seal, wherein the vent orifice is open; and orientingthe container such that the vent orifice is located above the dispensingopening, whereby the skin antiseptic composition flows into theapplicator.

In another aspect, the present invention provides a method of preparinga skin antiseptic composition dispenser for use by: providing a skinantiseptic composition dispenser having a container defining an interiorvolume, skin antiseptic composition located within the interior volumeof the container, an applicator attached to the container, and a liquidimpermeable sleeve, wherein the applicator is located within the liquidimpermeable sleeve; moving the skin antiseptic composition from thecontainer into the applicator, wherein the skin antiseptic compositionnot retained by the applicator is retained within the liquid impermeablesleeve; and removing the applicator from the liquid impermeable sleeveafter moving the skin antiseptic composition from the container into theapplicator.

These and other features and advantages of the invention may bedescribed more completely below in connection with various illustrativeembodiments of the skin antiseptic dispensers and methods of using them.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a cross-sectional view of one illustrative skin antisepticcomposition dispenser according to the present invention.

FIG. 2 is a cross-sectional view of a portion of another skin antisepticcomposition dispenser according to the present invention.

FIG. 3 is a cross-sectional view of one vent assembly for a skinantiseptic composition dispenser according to the present invention.

FIG. 4 is a cross-sectional view of another vent assembly for a skinantiseptic composition dispenser according to the present invention.

FIG. 5 is a view of another alternative pad shape for use in connectionwith a skin antiseptic composition dispenser according to the presentinvention.

FIG. 6 is a view of another alternative pad shape for use in connectionwith a skin antiseptic composition dispenser according to the presentinvention.

FIG. 7 is a view of another skin antiseptic composition dispenseraccording to the present invention.

FIG. 8 is a side view of the skin antiseptic dispenser of FIG. 7.

FIG. 9 is a view of another skin antiseptic composition dispenseraccording to the present invention.

FIG. 10 is a partial cross-sectional view of an applicator of a skinantiseptic dispenser in a sleeve according to the principles of thepresent invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS OF THE INVENTION

FIG. 1 is an illustrative embodiment of a skin antiseptic compositiondispenser that includes many aspects of the skin antiseptic compositiondispensers of the present invention. It should, however, be understoodthat all of the features depicted in the skin antiseptic compositiondispenser of FIG. 1 need not necessarily be present in all skinantiseptic composition dispensers according to the present invention. Inother words, the features of the skin antiseptic composition dispenserdepicted in FIG. 1 may be used in concert or various combinations of thefeatures may be employed to achieve some of the advantages possible inlight of the present invention.

The skin antiseptic composition dispenser 10 of FIG. 1 includes acontainer 20 that in the illustrative embodiment is in the form atubular shape with a wall 23 extending between ends 21 and 22. Thecontainer 20 may be in the form of a tube having a circularcross-section, although tubular containers with other cross-sectionalshapes may be used (e.g., oval, elliptical, hexagonal, rectangular,etc.). Tubes in the shape of right cylinders may, however, be desiredfor their stiffness, ease of manufacture, etc. Manufacturing thecontainers by extrusion may be useful to produce relatively thin (e.g.,wall thickness of less than 1000 micrometers, possibly less than 750micrometers, and possibly less than 500 micrometers) structures that mayalso function as barriers to sterilizing gases such as ethylene oxide.

The containers used in applicators of the present invention may be usedas handles. When used as a handle, the container may typically have anaspect ratio (i.e., length:diameter) of at least 2, in some instances atleast 4, and in other instances at least 6.

For use in preparation for a small surgical procedure, the amount ofskin antiseptic composition in the containers used in connection withthe present invention should generally be able to cover an area of,e.g., 10 square centimeters or more, and thus typically have volume of,e.g., 5-15 milliliters (ml). For larger surgical procedures, theapplicator should be able to cover at least the torso of a large person,e.g., at least about 500-600 square centimeters. To cover that largerarea, the container may typically have a volume of skin antisepticcomposition of at least 20 ml, preferably at least 25 ml, and morepreferably at least 30 ml.

The containers used in connection with the present invention may befilled with a skin antiseptic composition that includes (as theantimicrobial agent) iodine, an iodine complex, chlorhexidine,chlorhexidine salts, or combinations thereof. Preferred iodine complexesmay include iodophors, e.g., povidone-iodine USP. Preferredchlorhexidine salts may include, e.g., chlorhexidine digluconate andchlorhexidine diacetate. Other suitable antimicrobial agents may includeC2-C5 lower alkyl alcohols (including, e.g., ethyl alcohol, 1-propanol,and 2-propanol), parachlorometaxylenol (PCMX), triclosan,hexachlorophene, fatty acid monoesters of glycerin and propylene glycolsuch as glycerol monolaurate, glycerol monocaprylate, glycerolmonocaprate, propylene glycol monolaurate, propylene glycolmonocaprylate, propylene glycol moncaprate, phenols, surfactants, andpolymers that include a (C12-C22)hydrophobe and a quaternary ammoniumgroup, polyquaternary amines such as polyhexamethylene biguanide,quaternary ammonium silanes, silver, silver salts (such as silverchloride), silver oxide and silver sulfadiazine, methyl, ethyl, propyland butyl parabens, octenidene, peroxides (e.g., hydrogen peroxide andbenzoyl peroxide), and the like, as well as combinations thereof.

Among the challenges associated with using such skin antisepticcompositions is the need to sterilize the exterior of the applicatorwhile minimizing potential byproducts that may be produced when thecomposition is exposed to sterilization compounds such as ethylene oxidegas. Reactive sterilants such as ethylene oxide may react with theactive antimicrobial agent or with other components in the skinantiseptic composition altering the potency or producing potentiallytoxic compounds. For example, typical high density polyethylene bottleshaving wall thicknesses of less than about 500 micrometers allowethylene oxide through quite readily and result in iodophor preps havingiodohydrin levels of 100 parts per million (ppm) or more, in someinstances 200 ppm or more, and in some instances even as high as 600ppm.

Another challenge is that the effectiveness of the skin antisepticcompositions may be compromised by exposure to ethylene oxide gas. Forexample, iodine as well as other antimicrobial agents may potentiallyreact with ethylene oxide—which could alter the efficacy of the skinantiseptic composition.

To address these challenges, it may be advantageous to construct thecontainer wall or walls of a material or materials that are functionallyimpermeable to ethylene oxide gas. The material or materials selectedare also preferably capable of effectively storing a skin antisepticcomposition that includes iodine, an iodine complex, chlorhexidine,chlorhexidine salts or combinations thereof, as well as otherantimicrobial agents, for suitable time periods under typical storageconditions.

In addition to the above concerns, it may be desirable to provide acontainer that includes flexible walls free of metallic foil barrierlayers. As used in connection with the invention, “flexible walls” meanswalls that can be compressed or otherwise deformed by hand to dispensethe skin antiseptic composition located within the container withoutfracturing or leakage. As used in connection with the invention,“metallic foil barrier layers” means layers of metals or metalliccompounds that typically function as barriers to the passage ofconstituents in the skin antiseptic composition, e.g., gases, liquids,vapors, etc. The phrase “free of metallic foil barrier layers” shouldnot be construed to include layers that may include metallic particleslocated within, e.g., a polymeric binder, provided that the metallicparticles do not form a continuous metallic foil layer that acts as abarrier layer.

Another potential advantage of using containers free of metallic foilbarrier layers is that if a metallic foil layer such as, e.g., aluminumfoil, is exposed to a skin antiseptic composition containing iodine(e.g., an iodophor composition), the amount of iodine in the antisepticcomposition may be rapidly reduced. Exposure of the antisepticcomposition to metallic foil layers may be through, e.g., pinholes, orother defects in a coating that is otherwise meant to prevent directcontact between the antiseptic composition and the metallic foil layer.Reduction of the iodine levels in the antiseptic composition may beassociated with a reduction in the antiseptic efficacy of thecomposition.

Another potential advantage of containers made with walls that are freeof metallic foil barrier layers is that the walls may preferably betranslucent or transparent. Walls that are translucent or transparentmay allow for visual monitoring of the skin antiseptic compositionwithin the container. In contrast, walls that include metallic foilbarrier layers are typically opaque, thus preventing visual monitoringof the contents of the container.

In some embodiments, it may be desirable to include ceramic barriers toenhance the barrier properties of the flexible walls free of metallicfoil barrier layers. The flexible walls may, for example, include aceramic layer with a thickness of, e.g., 200 micrometers or less,possibly 100 micrometers or less, and in some cases 50 micrometers orless. Thinner ceramic barrier layers may enhance flexibility of thewalls. An example of such a ceramic barrier is marketed as CERAMIS(available from Alcan, Inc., Montreal, Canada). One potential advantageof containers with polymeric walls is that the containers may bemanufactured by polymer extrusion and lamination techniques.

In embodiments of the invention that include containers with flexiblewalls free of metallic foil barrier layers, the walls of the containersare preferably impermeable to liquid and vapor phases of the skinantiseptic composition located within the containers. It will beunderstood that the impermeability is not complete, i.e., some smallportion of one or more components within the skin antiseptic compositionmay pass through the walls of the containers, but the portions that passunder typical conditions will be functionally insignificant. Forexample, typical containers packaged as to be shipped (i.e., properlyfilled and sealed) placed in a convection oven at 60 degrees Celsius for14 days will typically lose 2% or less by weight of the contents, andpreferably 1% or less (with a sample size of at least five containers).

In addition to impermeability of the container walls, it is alsopreferred that, for those embodiments of containers used in connectionwith skin antiseptic compositions that are sensitive to ethylene oxideexposure (such as, e.g., iodine and other antimicrobial agents) theflexible walls exhibit a permeability to gaseous ethylene oxide of 20mg/hr/cm² or less. In some embodiments, the permeability to gaseousethylene oxide may be 10 mg/hr/cm² or less, possibly as low as 1mg/hr/cm² or less. The permeability to gaseous ethylene oxide ofpolymeric walls in containers of the present invention is determined inaccordance with the “Gaseous Ethylene Oxide Permeability” test describedbelow.

One example of a polymer wall construction that may be suitable forcontainers used with iodine-containing skin antiseptic compositions isdepicted in an enlarged cross-sectional view in FIG. 2. The depictedpolymeric wall is a multilayer construction including an inner layer 25,an optional intermediate layer 26, and outer layer 27. Although theinner layer 25, intermediate layer 26, and outer layer 27 are eachdepicted as a single homogenous layer, it will be understood that eachof those layers may include one or more sub-layers, particles,filaments, etc.

The inner layer 25 faces the interior volume of the container 20 and maypreferably provide an impermeable barrier to liquid and vapor phases ofone or more components of the skin antiseptic composition located withinthe container 20. In some embodiments, it may be preferred that theinner layer 25 also be capable of forming heat seal bonds either withitself (where, for example, the tube is compressed at one end to form aflat seal) or with other components inserted into, for example, an endof a cylindrical container. For example, the inner layer 25 may be apolyolefin (e.g., polyethylene such as high density polyethylene, etc.)that is a good barrier to water vapor and may also serve as a thermallysealable layer.

The outer layer 27 is located outside of the inner layer 25 relative tothe interior volume of the container 20. The outer layer 27 maypreferably provide the limited permeability to gaseous ethylene oxide asdiscussed above. Although the term outer layer is used herein, it shouldbe understood that the outer layer 27 may or may not form the actualexterior surface of the container. In other words, additional layers maybe provided as the exterior of the containers according to the presentinvention.

Gaseous ethylene oxide barrier layers may be the inner layer, outerlayer, and/or the intermediate layer. In FIG. 2, the outer layer 27 isthe barrier layer and may also be impermeable to one or more componentsof the skin antiseptic composition within the container 20. For example,a polyethylene terephthalate (PET) layer could be used to preventalcohol (e.g., ethanol or 2-propanol) in a skin antiseptic compositionfrom evaporating out of the container 20. When the antisepticcomposition contains alcohol, it may be preferred that at least onelayer of the container walls be manufactured of a material that isimpermeable to alcohol in the antiseptic compositions (as the term“impermeable” is described above).

The intermediate layer 26 may be provided to function as a tie layerbetween the inner layer 25 and the outer layer 27 where the materials ofthe inner layer 25 and the outer layer 27 will not exhibit sufficientattachment to each other. The intermediate layer 26 may be an adhesive,extruded polymeric layer, etc.

In one example of a suitable multilayer polymeric wall construction foruse in connection with the present invention, one of the inner layer 25and the outer layer 27 may be formed of polyolefin, e.g., polyethylene(including, but not limited to, low density polyethylene, linear lowdensity polyethylene, medium density polyethylene, high densitypolyethylene, metallocene polyethylenes, and mixtures thereof),polypropylene, ethylene/propylene copolymers, ethylene/butylenescopolymers, etc.

A second layer selected from the inner layer 25 and the outer layer 27may be formed of, e.g., polyesters (e.g., polyethylene terephthalate andpolybutylene terephalate), fluorinated layers such aspolytetrafluoroethylene (PTFE, e.g., TEFLON), polyamides (e.g., nylon),chlorotrifluoroethylene (ACLAR), polyvinylidene fluoride, as well ascopolymers of perflourinated monomers with partially fluorinatedmonomers such as copolymers oftetrafluoroethylene/hexafluoropropylene/vinylidene fluoride (THVFluorothermoplastic from Dyneon Company), polyvinylchloride,polyvinylidene chloride (PVDC, e.g., SARAN HB), ethylene vinyl alcohol(EVOH), polyolefins (e.g., polyethylene, high density polyethylene,polypropylene, and combinations thereof). Oriented and biaxiallyoriented polymers may be particularly preferred.

Particularly preferred barrier constructions include HDPE, PET, PETG,laminates of polyester and polyolefin (in particular PET/HDPE orHDPE/PET/HDPE), laminates of PET and EVOH, biaxially oriented nylon,PVDC, Nylon/EVOH/Nylon (OXYSHIELD OUB-R), chlorotrifluoroethylene andlaminates thereof, ceramic materials including silicon oxide (SiO_(x)where x=0.5-2 and preferably 1-2) coated thermoplastics, and ceramiccoated PET (CERAMIS available from CCL Container/Tube Division, OakRidge, N.J.).

The thickness of the barrier layer in each of these constructions ismaterial dependent. For single layer constructions in which HDPE is theonly component, the thickness of the HDPE layer is preferably 750micrometers or more, more preferably 1000 micrometers or more. Otherconstructions may be as thin as 25 micrometers or less. For example, oneconstruction found to work well was ACLAR 11A with a thickness of 25micrometers. A laminate of PET (37 micrometers) coated with HDPE (25micrometers on each side) also worked well. Other potentialconstructions are shown in the examples.

As depicted in FIG. 1, each end of the container 20 is preferably sealedto prevent fluids within the container 20 from escaping. At end 21, thecontainer 20 is optionally sealed by a vent assembly 30 that includes avent plug 32 secured in the end 21 of the container 20. The vent plug 32may be secured in the end 21 of the container 20 by any suitabletechnique, e.g., adhesively, by welding (chemical, spin, thermal,ultrasonic, etc.), a threaded seal with a gasket, etc.

The vent plug 32 includes a seal 34 over opening 35 in the vent plug 32.In the depicted embodiment, the opening 35 is located in the web 33 thatotherwise closes the passageway through vent plug 32. In someembodiments, the opening 35 may be the same size as the web 33, but itmay be preferred that the opening 35 be significantly smaller such thatexcessive amounts of fluids from within the container 20 cannot passthrough the opening 35 after the seal 34 has been pierced or otherwiseopened.

The vent assembly 30 also includes a cover 36 and associated piercingelement 37. The cover 36 may serve to at least partially protect theseal 34 from unwanted opening. In addition, the cover 36 may alsopreferably restrain the piercing element from opening the seal 34 untilopening of the seal 34 is desired. The piercing element 37 is designedto open the seal 34 by piercing, tearing, cutting, perforating, etc. Forexample, the piercing element may be in the form of a hollow circulardie that punctures or cuts open the seal 34.

In one embodiment, cover 36 may be threadably engaged with vent plug 32such that when cover 36 is screwed downward piercing element 37 opensseal 34. In another embodiment, cover 36 is slidably engaged with ventplug 32 such that when cover 36 is pushed downward piercing element 37opens seal 34. Other variations will be known to those of skill in theart of, e.g., packaging.

A variety of mechanisms may be used to maintain the attached, butspaced-apart relationship between the seal 34 and the piercing element37. For example, the cover 36 may be threadably engaged with the ventplug 32 or the container 20 itself. It may be preferred that detents orother structures be provided to prevent the cover 36 from disengagingwith the vent plug 32 after the cover 36 has been partially threadedthereon. In another alternative, the threads used to assemble the cover36 onto the vent plug 32 may be non-reversing. Any detents or otherstructures may also preferably restrain the cover 36 on the vent plug 32when partially threaded thereon to prevent unwanted or accidentaladvancement of the cover 36 on the vent plug 32 such that the piercingelement 37 does not unwantedly pierce the seal 34.

The vent assembly 30 as depicted in FIG. 1 is in a closed state in whichit preferably performs the function of sealing the end 21 of thecontainer 20 such that significant amounts of fluids within thecontainer 20 cannot escape therefrom and, likewise, significant amountsof fluids outside of the container 20, e.g., air or other gases, cannotenter the container 20. By significant amounts, it is meant that thepassage if small, infinitesimal amounts of gases and/or fluids may pass,but no functionally significant amounts which can alter the efficacy ofthe antiseptic prep will pass through the vent assembly 30 in its closedstate. For example, typical containers packaged as to be shipped (i.e.,properly filled and sealed) placed in a convection oven at 60 degreesCelsius for 14 days will typically lose 2% or less by weight of thecontents, and preferably 1% or less (with a sample size of at least fivecontainers).

FIG. 3 depicts the cover 36 after advancement onto the vent plug 32 by asufficient distance to cause the piercing element 37 to open the seal34. Furthermore, it may be preferred that after advancement of the cover36 onto the vent plug 32, detents or other structures be provided torestrict or prevent reversal of the advancement of the cover 36 onto thevent plug 32. If the cover 36 is threadably engaged with the vent plug32, rotation of the cover 36 about the axis 12 will cause the piercingelement 37 to move in an arc about the axis 12 which may contribute toopening of the seal 34 as the cover 36 is rotated.

Cover 36 may be designed such that piercing element 37 comprises a ventpassage or a vent passage may be provided elsewhere in cover 36.Preferably a deliberate vent passage such as a vent hole is provided torestrict the entry of air into the container so that the antisepticcomposition does not flow out of the container 20 too rapidly. If theflow out of the container 20 is too rapid, it may cause unwanteddripping from the applicator. While it may be desired to limit the rateof flow out of the container 20, it is may also be desirable to providevent holes have a sufficiently large diameter such that the antisepticcomposition flows out of the container at a rate that is not too slowfor use during, e.g., surgical procedures.

When balancing the desire for flow out of the container that is not toorapid or too slow, it may be preferred that the skin antisepticcomposition be capable of flowing out of the container within 60 secondsor less, preferably 45 seconds or less, and possibly more preferably 30seconds or less.

Vent holes suitable for use with applicators containing antisepticcompositions with viscosities of, e.g., 5-10 centipoise or less (e.g.,aqueous compositions) that are dispensed to the interior of an open cellhydrophilic foam, may, for example, have a diameter of 2500 micrometersor less, more preferably 2000 micrometers or less, and most preferably1800 micrometers or less. At the lower end, suitable vent holesdiameters may be, e.g., 500 micrometers or more, preferably 750micrometers or more, or possibly 1000 micrometers or more.

Until pierced or otherwise opened, the seal 34 prevents fluids fromwithin the container 20 escaping through the opening 35. Likewise, theseal 34 preferably prevents fluids, e.g., air, sterilants (such asethylene oxide), etc., from entering the container 20 until the seal 34is pierced or otherwise opened. The seal 34 itself may be constructed ofa variety of materials. The seal 34 may include barrier materialssimilar to those chosen for the container walls, although the seal 34may also include metallic foil laminates, e.g., aluminum foil laminates.It may be preferred that the foil laminates include a thermally sealablepolyolefin layer, a polyester layer, a aluminum foil layer and one ormore intermediate tie layers TRISEAL TS-PE/1, available from Tekni-plex,Flemington, N.J. As an alternative to a metallic foil laminate, the seal34 may be constructed as a laminate of two or more polymeric layers, itmay be only a metallic layer, or any other suitable construction capableof providing the barrier properties described herein. In anotheralternative, the seal 34 may be manufactured with the same constructionas the container walls as described above.

The seal 34 may be attached to the container 20 by any suitabletechnique, such as, adhesively, thermally (by, e.g., heat sealing,thermal welding, ultrasonically, etc.), chemical welding (using, e.g.,solvents), etc.

In the depicted embodiment, the size of the opening 35 is used torestrict the passage of fluids through the vent assembly after openingof seal 34. Alternatively, the interior of the vent plug 32 could beopen, i.e., not include a restricted opening 35, and the cover 36 andvent plug 32 could be designed to offer one or more restrictedpassageways to the passage of fluids after opening of the seal 34(through, e.g., loose thread structures, etc.).

In another alternative for a vent assembly 30 used in connection with askin antiseptic composition dispenser according to the presentinvention, it may be possible to replace a threaded vent plug 32 andcover 36 with, e.g., a bayonet-mount cover that provides for the desiredfunction of restraining the piercing element 37 from opening the seal 34until desired. The bayonet-mount may also provide for retention of thecover 36 on the vent plug 32 after opening of the seal 34. Othermechanisms capable of protecting the seal 34, restraining the piercingelement 37, and retaining the cover 36 on the vent plug after opening ofthe seal 34 may be envisioned in place of the illustrative embodimentsspecifically described herein.

It may also be desirable to avoid “pinch points” on the dispensers ofthe present invention. A pinch point is a location where components inthe dispenser come together in a manner that could pinch or otherwisecapture a user's skin, surgical glove, clothing, etc. With respect todispenser 10, pinch points may be avoided by providing a skirt 39 as apart of the cover 36 as seen in, e.g., FIGS. 1 and 3. The skirt 39extends over any threads or pinch points that would otherwise be exposedbefore the cover 36 is advanced to open the seal 34. Although notdepicted, a skirt could be provided on the dispensing assembly 40 tocover any exposed threads or pinch points.

One example of another vent assembly 130 that does not include apiercing element is depicted in FIG. 4, where the end 121 of a container120 is depicted along with a removable seal 134 on vent plug 132. Theseal 134 covers opening 135 in the vent plug 132. The depicted seal 134includes an optional tab 139. The tab 139 can be grasped and pulled toremove the seal 134 from vent plug 132. With the seal 134 removed,opening 135 provides a passageway into container 120 for air or otherfluids. Although not depicted, vent plug 132 may include a one-way valvesuch that fluids can enter container 120 through opening 135 but theexit of fluids from container 120 through opening 135 is restricted.

Turning to the opposite end 22 of the container 20, one example of adispensing assembly 40 that can be used in connection with the skinantiseptic composition dispensers of the present invention is depicted.The dispensing assembly 40 includes a barrier plug 42 located in the end22 of the container 20. The barrier plug 42 may be secured in the end 22of the container 20 by any suitable technique, e.g., adhesively, bywelding (chemical, spin, thermal, ultrasonic, etc.), by a threaded sealwith a gasket, etc.

The barrier plug 42 includes a seal 44 over an opening 45 in the barrierplug 42. Until pierced or otherwise opened, the seal 44 prevents fluidsfrom within the container 20 escaping through the opening 45. Likewise,the seal 44 preferably prevents fluids, e.g., air, from entering thecontainer 20 until the seal 44 is pierced or otherwise opened. The seal44 itself may be constructed of a variety of materials. For example, theseal 44 may be formed of a laminate including a metallic foil (e.g.,aluminum/polymer laminates, one of the container wall constructions, orany other suitable construction as discussed in connection with seal 34above. The seal 44 may be attached by any suitable technique, e.g.,adhesively, thermally (by, e.g., heat sealing, thermal welding,ultrasonically, etc.), chemical welding (using, e.g., solvents), etc.

The dispensing assembly 40 also includes a dispensing tip 46 andassociated piercing element 47. The dispensing tip 46 may serve to atleast partially protect the seal 44 from unwanted opening. In addition,the dispensing tip 46 may also preferably restrain the piercing element47 from opening the seal 44 until opening of the seal 44 is desired. Thepiercing element 47 may include a barb used to open the seal 44 bypiercing, tearing, cutting, perforating, etc. For example, the piercingelement may be in the form of a hollow circular die that punctures orcuts open the seal 44. The dispensing tip 46 also includes openings 48formed therein that allow the skin antiseptic composition located withincontainer 20 to pass therethrough after the seal 44 has been opened.

A variety of mechanisms may be used to maintain the attached, butspaced-apart relationship between the seal 44 and the piercing element47. For example, the dispensing tip 46 may be threadably engaged withthe barrier plug 42 or the container 20 itself. It may be preferred thatdetents or other structures be provided to prevent the dispensing tip 46from disengaging with the barrier plug 42 after the dispensing tip 46has been partially threaded thereon. In another alternative, the threadsused to assemble the dispensing tip 46 onto the barrier plug 42 may benon-reversing. Any detents or other structures may also preferablyrestrain the dispensing tip 46 on the barrier plug 42 when partiallythreaded thereon to prevent unwanted or accidental advancement of thedispensing tip 46 on the barrier plug 42 such that the piercing element47 does not unwantedly pierce the seal 44.

The dispensing assembly 40 as depicted in FIG. 1 is in a closed state inwhich it preferably performs the function of sealing the end 22 of thecontainer 20 such that significant amounts of fluids within thecontainer 20 cannot escape therefrom and, likewise, significant amountsof fluids outside of the container 20, e.g., air or other gases, cannotenter the container 20. By significant amounts, it is meant that smallamounts of gases and/or fluids may pass, but no functionally significantamounts will pass through the dispensing assembly 40 in its closedstate.

After advancement of the dispensing tip 46 onto the barrier plug 42towards end 21 of the container 20 by a sufficient distance, thepiercing element 47 pierces or otherwise opens the seal 44. It may bepreferred that after advancement of the dispensing tip 46 onto thebarrier plug 42, detents or other structures be provided to restrict orprevent reversal of the advancement of the dispensing tip 46 onto thebarrier plug 42. Because the depicted dispensing tip 46 is threadablyengaged with the barrier plug 42, rotation of the dispensing tip 46about the axis 12 causes the piercing element 47 to move in an arc aboutthe axis 12 which may contribute to opening of the seal 44 as thedispensing tip 46 is rotated relative to the seal 44.

If both the cover 36 of the venting assembly 30 and the dispensing tip46 of dispensing assembly 40 are threadably engaged with the skinantiseptic composition dispenser 10 at opposing ends of container 20, itmay be desirable if the threads are provided such that a user can rotatethe cover 36 and tip 46 in opposite directions about axis 12 tosimultaneously open the seals 34 and 44 at opposing ends of thecontainer 20.

In the depicted skin antiseptic composition dispenser 10, an applicator50 is located over the openings 48 on dispensing tip 46. As a result,the skin antiseptic composition passes through the openings 48 and intothe interior of the applicator 50 when the seal 44 is opened. Theapplicator 50 may be made of a variety of materials, e.g., foam,non-woven fibrous masses, woven or knitted structures, stitchbondedstructures, etc.

It may be preferred that the applicator 50 be made of a material ormaterials that retain fluids, e.g., by absorption, adsorption, etc. Oneexample of a potentially preferred material is an open-cell polyurethanefoam.

It may, however, be preferred that the applicator 50 be constructed of afoam pad capable of passing fluids therethrough. In some instances, itmay be preferred that the applicator 50 be constructed of a relativelyhydrophilic foam. The hydrophilic foam may, e.g., have an apparentsurface energy of 35 dynes/centimeter or more. Even higher apparentsurface energy may be desirable in connection with some skin antisepticcompositions, e.g., apparent surface energy of 40 dynes/centimeter ormore may be preferred. It may, however, be preferred that thehydrophilic foams used as applicators in the present invention have anapparent surface energy of 45 dynes/centimeter or more, possibly 50dynes/centimeter or more. In some instances, it may be preferred thatthe hydrophilic foam be wettable by deionized water (thus having, e.g.,an apparent surface energy of 70 dynes/centimeter or more). Unlessotherwise indicated, apparent surface energy is determined according tothe “Apparent Surface Energy Test” procedure described herein.

Surprisingly, hydrophilic foams used with aqueous skin antisepticcompositions provide superior antimicrobial efficacy as compared totraditional hydrophobic foams. Similar efficacy enhancement may bepossible for aqueous enhancement may be possible for aqueous antisepticsapplied using foam scrub brushes for use in, e.g., disinfecting thehands of a clinician (e.g., doctor, nurse, etc.).

It may be preferred that the minimum distances between the openings 48in the dispensing tip 46 and the outer surface of the applicator 50 begenerally consistent. Uniformity in the minimum distances between theopenings 48 and the outer surface of the applicator 50 may reduce thetendency of the skin antiseptic composition to drip from the applicator50 during dispensing of the skin antiseptic composition.

It may also be useful to control the size and distribution of theopenings 48 in the dispensing tip 46 to preferably uniformly fill theapplicator 50. Suitable dimensions for the openings 48 may be, e.g., 5millimeters (mm) to 6.5 mm. The size and distribution of the openings 48may vary based on a variety of factors, e.g., the porosity and apparentsurface energy of the applicator 50 surrounding the dispensing tip 46,the viscosity and surface tension of the skin antiseptic compositionwithin the container 20, the number of openings 48 in the tip 46, etc.

The applicator 50 may take a variety of different shapes depending onthe intended use of the skin antiseptic composition dispenser 10. Onesuitable shape for an applicator 50 may be, e.g., a circular cylindricalshape as depicted in FIG. 5. It may be preferred that cylinder be aright cylinder as depicted, although oblique cylinders may also beprovided.

Another variation on the shape of the applicators used in connectionwith the skin antiseptic composition dispensers of the present inventionis depicted in FIG. 6. The applicator 150 depicted as a part of skinantiseptic composition dispenser 110 is in the form of a truncated conewith circular bases at each end.

Still another variation in the shape of an applicator used in connectionwith a skin antiseptic composition dispenser according to the presentinvention is depicted in FIGS. 7 & 8. The applicator 250 of skinantiseptic composition dispenser 210 includes two opposing majorsurfaces 252 separated by an edge surface 254. The edge surface 254 maybe flat as shown, although other edge profiles may also be used in placeof the flat profile shown.

FIG. 8 illustrates another potential feature of the applicators used inconnection with skin antiseptic composition dispensers of the invention.The container 220 is elongated such that it defines a longitudinal axis212 along its length. Although the major surfaces 252 may be located inplanes that are generally parallel to the axis 212, it may be preferredthat the major surfaces 252 be located in planes that are not parallelwith the longitudinal axis 212 of the container 220. The major surfaces252 of the illustrated applicator 250 are canted to form angle β (beta)with the longitudinal axis 212 in FIG. 7. The angle β (beta) may be,e.g., 2.5 degrees or more, preferably 5 degrees or more (although thisis somewhat dependent on the length of the applicator 250 and themorphology of the container 220 connected thereto).

When the major surfaces of applicators are described herein as beinglocated in a plane or defining a plane, it should be understood that themajor surface need not necessarily be planar itself. Rather, the majorsurface may deviate somewhat from true planar surface, e.g., it may beslightly curved, undulating, or include various other deviations from atrue planar surface.

A potential advantage of providing an applicator 250 with a canted majorsurface 252 is that during use on, e.g., the skin of a patient, thecontainer 220 (which serves as the handle) is spaced from the patient'sskin when the surface 252 is resting flat on the skin. As a result,clearance may be provided between the user's hand and the patient'sskin. That clearance can reduce the likelihood of contact between theuser's hand and the patient's skin, thereby improving aseptic techniquein use of the skin antiseptic composition dispenser 210. If theapplicator 250 is soft and/or conformable (such as a foam), the cantedmajor surfaces 252 will not typically prevent the dispenser 210 frombeing used to dispense skin antiseptic composition within body orifices,e.g., vagina, rectum, etc.

Among the variations in applicators that may be described with respectto FIGS. 7 & 8, one variation in applicator design may include majorsurfaces that are canted at different angles from the longitudinal axis212. In another variation, one of the major surfaces may be located in aplane that is parallel to the longitudinal axis 212, while the othermajor surface is canted relative to the longitudinal axis 212.

When the container 220 is in the form of an elongated tubular shape, itmay be preferred that the major surfaces 252 be positioned such that thelongitudinal axis 212 defined by the container 220 does not intersectone or both of the major surfaces 252.

FIG. 9 depicts another variation in applicators used in connection withthe skin antiseptic composition dispensers. The applicator 350 of skinantiseptic composition dispenser 310 includes two major surfaces 352that, in the depicted embodiment, are generally parallel with eachother. The lower surface 352 is located in a plane that forms an angle α(alpha) with the longitudinal axis 312 defined by the container 320. Thecanted applicator 350 may be useful in providing clearance between auser's hand on the container 320 and a patient's skin during dispensingof the skin antiseptic composition within the container 320. The angle α(alpha) may preferably be 15 degrees or less, in some instances 10degrees or less. At the opposite end of the range, it may be preferredthat angle α (alpha) be 5 degrees or more.

FIG. 10 depicts another optional feature of some embodiments of skinantiseptic composition dispensers of the present invention. The skinantiseptic composition dispenser 410 includes an applicator 450 at oneend. The applicator 450 is, however, located in a sleeve 460. The sleeve460 is preferably made of materials (e.g., films, etc.) that areimpermeable to the skin antiseptic composition located within thecontainer 420. As a result, when the skin antiseptic composition isdelivered to the applicator 450 while the applicator 450 is locatedwithin sleeve 460, any of the skin antiseptic composition that escapesfrom the applicator 450 is retained within sleeve 460.

Furthermore, the sleeve 460 may be grasped by the user to pierce theseal(s) and dispense the antiseptic composition into the applicator. Thesleeve 460 can then be removed to reveal the applicator. In this manner,the applicator is easily filled with the antiseptic composition withoutcontamination of the applicator by the hands of the user.

The sleeve 460 is preferably retained around the applicator 450 untilits removal is desired. Retention of the sleeve may be effected by asleeve 460 that is sized to fit tightly on the applicator 450.Alternatively, the sleeve 460 may include spot welds, adhesives, orother materials/structures that assist in retaining the sleeve 460 onthe applicator 450 until its removal is desired.

In one method of using a sleeve 460 in connection with a skin antisepticcomposition dispenser 410, the skin antiseptic composition withincontainer 420 is dispensed into the applicator 450 by any suitabletechnique (e.g., squeezing the container 420, allowing the skinantiseptic composition to drain into applicator 450 under the force ofgravity, etc.). Any of the skin antiseptic composition that wouldotherwise drip from the applicator 450 is captured within the sleeve460. After the skin antiseptic composition is dispensed from thecontainer 420, the sleeve 460 and applicator 450 located therein may becompressed and released. Typically, that compression and releasesequence will result in substantially all of the skin antisepticcomposition returning into the applicator 450 (particularly where theapplicator 450 is constructed of a hydrophilic foam). Afterwards, thesleeve 460 can be removed from the applicator 450, which is then readyfor use in dispensing the skin antiseptic composition to a patient.Sleeves intended for use in the manner just described are preferablyflexible to allow compression of the applicator 450 as just described.

The volume of the sleeve 460 is preferably at least as great as thevolume of the skin antiseptic composition in the container 420.Typically, although not necessarily, the volume of the sleeve 460 willbe at least 200% of the volume of the skin antiseptic composition in thecontainer 420. It may be preferred that volume of the sleeve 460 be 300%or more of the volume of the skin antiseptic composition within thecontainer 420. The volume of the sleeve is measured with an emptyapplicator pad fully inserted into an upright sleeve having nodispensing tip attached. The mass of water that can just fill the sleeveis recorded and converted to volume assuming a density of 1 g/cm³. Thevolume of the sleeve should not be so great that the sleeve interfereswith activating the dispenser. For example, in some embodiments thedispensing tip 46 is rotated relative to the container to open thedispensing seal 44. A sleeve that extends too far up the container wouldmake it inconvenient to grasp the sleeve covered applicator pad in onehand and the container in the other without inadvertently grasping thesleeve.

Furthermore, it should be noted that the sleeve 460 is preferably openon the end facing the container 420 so that the sleeve 460 can retainany excess antiseptic composition and yet be easily removed.Furthermore, the opening in sleeve 460 allows a sterilant gas (e.g.,ethylene oxide) to enter and sterilize the foam and be easily removed byaeration after the sterilization is complete.

The applicator 450 covered with sleeve 460 on the dispenser 410 may befurther packaged in an outer package such as a bag, pouch, box, etc.,that is permeable to sterilants such as ethylene oxide. In this manner,the entire exterior of the dispenser 410 can be sterilized. In use, theclinician removes the outer package and aseptically delivers thesleeve-covered applicator 450 to the sterile field. The antisepticcomposition in the container 420 is released into the applicator 450 anddistributed by massaging the sleeve-covered applicator 450 (ifnecessary). Finally, the sleeve 460 is removed and the antiseptic isapplied to the patient using the applicator 450, with the container 420acting as the handle.

In embodiments where the applicator and dispensing tip are threadably orslidably engaged with the container, the sleeve 460 is preferablysufficiently stiff to prevent getting caught in the mechanism duringactivation. For sleeves made of low density polyethylene, the sleevethickness may be, e.g., greater than 50 micrometers, more preferablygreater than 75 micrometers, and most preferably greater than 85micrometers.

Test Protocols

The following test protocols may be used to determine the physicalproperties discussed above with respect to the invention.

Gaseous Ethylene Oxide Permeability Test

The permeation of ethylene oxide (ETO) across various polymer films overa given unit area for a specified amount of time was measured using thefollowing procedure. A known thickness of film was clamped between twoglass test chambers (1.6 inches (4.06 cm) in diameter at the base),which were sealed to the film with an o-ring on either side. A cylinderof 100 percent ETO was placed upstream of the film under a pressure of60 psi (0.41 MPa) and a slow, 10 ml/hr, flow of ETO was allowed to passthrough the upstream chamber while the downstream chamber was swept withnitrogen gas at 40 ml/hr through a charcoal adsorption tube for 2 hours.The 8 mm×100 mm charcoal tube contained 20228 ORBO Coconut shellcharcoal in two sections, front (400 mg) and back (200 mg) and iscommercially available from Supelco, Bellefonte, Pa.

Ideally the ETO is trapped on the front portion. The back is analyzed toshow that most if not all of the ETO is found on the front. Ifsignificant ETO (>10%) is found on the back portion it suggests that thetube was overloaded and that some ETO has passed through.

The individual sections were removed from the sampling tube andextracted for more than 2 hr with 2.0 mL acetone to desorb the ETO.

The extract solutions were analyzed by gas chromatography (GC) using thefollowing equipment and conditions:

Instrument: Agilent Technologies 6890 GC or 5890 GC or equivalent

Column. Agilent HP-INNOWAX 30 m×0.25 mm 0.5μ film

Carrier: Helium at 1.6 mL/min

Injection: 1 μL split 1/20 (200° C.)

Oven program: 30° C. (4 min hold) then at 20° C./min to 240° C. (hold 10min)

Detection: Flame ionization (240° C.)

Under these conditions the ethylene oxide eluted as a peak at 2.0+/−0.1minutes. A reference solution of ETO was prepared by collecting knownvolumes of ethylene oxide gas at room temperature and pressure. This wasinjected into a sealed vial containing a known volume of acetone, inwhich it was extremely soluble. A series of standard solutions of knownconcentrations was made by serial dilution of this standard withacetone.

The standards were injected under the same conditions as the sampleextracts so a calibration curve of peak area vs. ETO concentration wasset up. The sample concentrations were estimated by interpolation of thepeak area values on this curve. Thus ETO permeation (mL/hr/in²)=(ETOextract concentration×(mL gas/mL solution))×(extract solution volume(mL))/(Film area (in²))×(Test time (hr))

Where: extract solution volume=2 mLFilm area=1.227 in² (7.916 cm²)Test time=2 hrs

The ETO permeation was converted from mL ETO/hr/in² to mL ETO/hr/cm².Then using ETO density equal to 0.882 g/cc, ETO permeation was convertedto mg ETO/hr/cm² and divided by the film thickness in micrometers togive mg of ETO/hr/cm²/μm.

Gaseous Ethylene Oxide Residuals Test

Small (3 in (7.62 cm) by 5 in (12.70 cm)) dual heat sealed pouches wereconstructed with a seal line width of 0.48 cm from the first 12 filmslisted in Table 1a. The pouches were filled with 25 ml of tap water andexposed to a standard ETO sterilization cycle in 3M STERIVAC 4XL ETOSterilizer, 3M, St. Paul, Minn. The sterilization cycle was for 4.5hours of exposure to ETO at 37° C. with a 2.25-hour aeration time.

The contents of the pouches were removed and analyzed for ETO residualand conversion products, ethylene chlorohydrins (ECH) and ethyleneglycol (EG) using ANSI/AAMI/ISO 10993-7 Biological Evaluation of MedicalDevices—Part 7: Ethylene oxide sterilization and ANSI/AAMI St30:Determining Residual Ethylene Chlorohydrins and Ethylene Glycol inMedical Devices by Biotest Laboratories, Inc. Minneapolis, Minn. Theresults were reported in parts per million (ppm)

Apparent Surface Energy Test

The method for measuring the surface energy was AATCC Test Method118-1983, with the modifications described below. Surface energiesmeasured according to this modified test method are referred to hereinas “apparent” surface energies. The modified AATCC test method 118-1983determines the surface energy of a fabric or foam by evaluating theapplicator's resistance to wetting by a series of selectedmethanol/water compositions. By employing various mixtures of methanoland water in the applicator resistance test, the measurement of a rangeof surface energies may be accomplished. Surface tension values wereextrapolated from data given in Handbook of Chemistry and Physics56^(th) ed. page F-42, CRC Press, by plotting the data and generating aregression curve using the following formula: surfacetension=−0.0000777x³+0.0163756x²−1.3499137x+71.1475488 where x=percentvolume of methanol.

The compositions and their representative surface tensions are asfollows:

Liquid Volume percent Surface Tension No. Methanol/Water (dynes/cm at20° C.) 1 80/20 28 2 70/30 30 3 57/43 33 4 46/54 36 5 39/61 39 6 32/6842 7 27/73 45 8 24/76 47 9 20/80 50 10 14/86 55 11  9/91 60 12  0/100 72

The test procedure was as follows. A specimen of the applicator foammaterial was placed such that the major surface used for testing washorizontal. For convenience the tests were conducted at 23-25° C. (roomtemperature) at approximately 50% relative humidity. Using the method ofAATCC 118-1983 except that beginning with the lowest surface tensiontest liquid shown above, five drops of the test liquid were gentlyplaced on the surface of the applicator. Note that the drop was placedon the surface, i.e. not allowed to fall onto or impact the surface. Ifthe applicator was not homogeneous, (e.g., was a laminate or othernon-homogeneous construction), the test liquid was placed in variouslocations on the surface that faced the impregnating antisepticcomposition. If three of the five drops wicked into the applicatorwithin 60 seconds, the test liquid of the next higher surface energy wasused. When at least 3 drops remained on the applicator surface, theapparent surface energy was recorded as the value of the highestnumbered liquid which had at least 3 drops absorb. (For a liquid to weta surface the surface tension of the liquid must be less than thesurface energy of the solid. More precise determination of the apparentsurface energy could be accomplished by preparing fluids with surfacetensions intermediate those numbered fluids shown in the table above.)

Human Skin Antimicrobial Activity

Two formulations were checked for antimicrobial activity in a methodsimilar to ASTM Test Method E-1173-93 Standard Test for Evaluation of aPre-operative Skin Preparation, except that the compositions wereapplied to the backs (considered a “dry” site) of healthy volunteers andthe baseline bacterial flora counts as put forth in section 7.1 of theASTM method were not as high. Preps were always compared to the 2-stepapplication of BETADINE Surgical Scrub (7.5% povidone-iondine, PurdueFrederick Company, Norwalk, Conn.) and BETADINE Surgical Solution (10%povidone-iodine “paint”, Purdue Frederick Company, Norwalk, Conn.) perthe manufacturer's instructions. All studies were randomized blockdesigns.

On the Study Day, two samples for baseline microbial counts were taken,one from the upper back and one from the lower back, on opposite sidesof the spine. The test formulations and the control were randomized onthe back-usually four across the upper back and four across the lowerback. The residual bacteria were sampled from all sites 2.0 minutesafter completion of application. Formulations were applied using each oftwo sponges, Sponge No. 3 on the applicator tip and Sponge No. 4 on itssponge stick, as described in Example 5. The prep was applied by simplypainting a 2×5 inch (5.08×12.7 cm) stripe with moderate pressure in aback and forth motion for 30 seconds (approximately 30 times). BETADINESurgical Scrub and BETADINE Surgical Solution were applied followingmanufacturer's directions. Briefly, BETADINE Surgical Scrub was appliedwith saturated gauze and scrubbed for 5 minutes, wiped off; and theBETADINE Surgical Solution applied in an outward spiral from center.

Minimums of 8 subjects were used in accordance with sections 8.2-8.3 ofASTM testing method E1173. All subjects refrained from usingantimicrobial products for a minimum of 2 weeks. The average logreduction from baseline was determined for each composition. If multiplesites were run, the log reduction for each site was determined Resultswere reported in average log reductions (numerical average of the logreduction values).

Note that an appropriate neutralizer was first determined for eachformulation tested in accordance with ASTM testing method E1173-93section 6.7. For most polymer systems the following neutralizingsampling solution was used: 0.4 g potassium dihydrogen phosphate, 10.1 gsodium hydrogen phosphate, 1.0 g TRITON X100 surfactant available fromUnion Carbide Corp., Houston Tex., 4.5 g lecithin (CAS #8002-43-5,available from Fisher Scientific, Fairlawn, N.J. as Cat No. 03376-250),45.0 g TWEEN 80 (ICI), 1.0 g sodium thiosulfate, and deionized water tobring the total volume to 1 liter. The sampling solution was prepared byadding all components together and heating with stirring toapproximately 60° C. until dissolved. It was then placed in containersand steam sterilized.

GLOSSARY

Acronym Chemical Description EVOH Ethylene-vinyl alcohol PETGPolyethylene terephthalate glycol, modified PP Polypropylene HDPE Highdensity polyethylene PVDC Polyvinylidene chloride PET Polyethyleneterephthalate EVA Ethylene vinyl acetate ETO Ethylene oxide ECH Ethylenechlorohydrins EG Ethylene glycol CXA Co extruded Adhesive

EXAMPLES Example 1

Commercially available thermoplastic films of varying thickness wereevaluated for ETO permeability using the Gaseous Ethylene OxidePermeability Test described above. The descriptions of twenty-nine ofthe more useful films evaluated are shown in Table 1a and the thicknessof the films and results of the ETO permeability test are shown in Table1b.

A sample circle was cut from each of two bottles. One bottle was madefrom HDPE (commercially available as FORTIFLEX B53-35H-011 natural fromSolvay Polyethylene North America, Houston, Tex.) and the other bottlewas PP/EVOH/PP/PP and was used for bottling ketchup (commerciallyavailable from H. J. Heinz, Pittsburgh, Pa.). The samples were evaluatedusing the Gaseous Ethylene Oxide Permeability Test. The thickness of thesample and results of the ETO permeability test are shown in Table 1b.

TABLE 1a Description of Commercially Available Films Film Chemical NoProduct Name Description Source, Address 1 OXYSHIELD Nylon/EVOH/ AlliedSignal OEB nylon Morristown, NJ 2 OXYSHIELD Nylon/EVOH/ Allied SignalOEB nylon Morristown, NJ 3 OXYSHIELD Nylon/EVOH/ Allied Signal OEB-Rnylon Morristown, NJ 4 OXYSHIELD Nylon/EVOH/ Allied Signal OUB-R nylonMorristown, NJ 5 ACLAR 33C Fluoropolymer Allied Signal Morristown, NJ 6ACLAR 33C Fluoropolymer Allied Signal Morristown, NJ 7 ACLAR 22AFluoropolymer Allied Signal Morristown, NJ 8 ACLAR 22A FluoropolymerAllied Signal Morristown, NJ 9 ACLAR 11A Fluoropolymer Allied SignalMorristown, NJ 10 ACLAR 11A Fluoropolymer Allied Signal Morristown, NJ11 PACUR 6763 PETG Pacur Oshkosh, WI 12 PACUR 6763 PETG Pacur Oshkosh,WI 13 360 HB-2 Oriented PP QPF Streamwood, IL 14 250 HB-2 Oriented PPQPF Streamwood, IL 15 225HBHE Oriented PP QPF Streamwood, IL 16BARRIALON 26 HDPE/PVDC/ Phoenix Films, Clearwater, HDPE FL (Distributor)Asahi Chemical Industry Co., Tokyo, Japan 17 BARRIALON 50 PVDC PhoenixFilms, Clearwater, FL (Distributor) Asahi Chemical Industry Co., Tokyo,Japan 18 BARRIALON 56 PP/PVDC/PP Phoenix Films, Clearwater, FL(Distributor) Asahi Chemical Industry Co., Tokyo, Japan 19 3M DMT ClearPET 3M, St. Paul, MN 20 Film Plus HDPE/PET/ Loparex, Inc., HDPEWillowbrook, IL 21 3M SCOTCHPAK PET/EVA 3M, St. Paul, MN 135 22 CAPRANDF Nylon Allied Signal Morristown, NJ 23 CAPRAN Biaxial Oriented AlliedSignal EMBLEM 2500 nylon Morristown, NJ 24 PET-SiOx PET/Silicon PhoenixFilms, Clearwater, Oxide FL (Distributor) Asahi Chemical Industry Co.,Tokyo, Japan 25 ACLAR 22C Fluoropolymer Allied Signal, Morristown, NJ 26SCOTCHPAK PET/EVA 3M, St. Paul, MN 29312 27 SCOTCHPAK 6 PET/LDPE 3M, St.Paul, MN 28 SCOTCHPAK 33 PET/EVA 3M, St. Paul, MN 29 BARRIALON 25PVDC/HDPE Phoenix Films, Clearwater, FL (Distributor) Asahi ChemicalIndustry Co., Tokyo, Japan

TABLE 1b Film Thickness and Results of Ethylene Oxide Permeation TestThickness ETO Permeation Film ml ETO/hr/in² mg ETO/ mg ETO/hr/ Numbermils(microns) (ml ETO/hr/cm²) hr/cm² cm²/micron 1  0.60 (15.24) 0.085(0.0132) 11.620 0.762 2  1.00 (25.40) 0.062 (0.0096) 8.476 0.334 3  1.00(25.40) 0.013 (0.0020) 1.777 0.070 4  1.00 (25.40) 0.009 (0.0014) 1.2300.048 5  0.78 (19.81) 0.028 (0.0043) 3.830 0.193 6  2.00 (50.80) 0.017(0.0026) 2.324 0.046 7  0.75 (19.05) 0.012 (0.0019) 1.640 0.086 8  3.00(76.20) 0.111 (0.0172) 15.175 0.199 9  1.00 (25.40) 0.018 (0.0028) 2.4610.097 10  0.60 (15.24) 0.016 (0.0025) 2.187 0.144 11 10.00 (254.00)0.015 (0.0023) 2.051 0.008 12  5.00 (127.00) 0.047 (0.0073) 6.425 0.05113  0.80 (20.32) 0.047 (0.0073) 6.425 0.316 14  1.22 (30.99) 0.058(0.0090) 7.929 0.256 15  1.36 (34.54) 0.022 (0.0034) 3.008 0.087 16 2.60 (66.04) 0.009 (0.0014) 1.230 0.019 17  2.00 (50.80) 0.002 (0.0003)0.273 0.005 18  2.40 (60.96) 0.018 (0.0028) 2.461 0.040 19  1.50 (38.10)0.001 (0.0002) 0.137 0.004 20 Total: 3.00 0.010 (0.0016) 1.367 0.018(76.20) By layer: 0.75/1.50/0.75 (19.05/38.10/ 19.05) 21  0.86 (21.84)0.001 (0.0002) 0.137 0.006 22  1.00 (25.40) 0.001 (0.0002) 0.137 0.00523  0.98 (24.89) 0.001 (0.0002) 0.137 0.005 24  0.48 (12.19) 0.001(0.0002) 0.137 0.011 HDPE 80.00 (2030) 0.015 (0.0023) 2.05 0.0032Bottle¹ Sample PP/ 60.00 (1520) 0.077 (0.012) 10.5 0.021 EVOH/ PP/PPBottle² Sample ¹HDPE bottle was blown from FORTIFLEX B53-35H-011 naturalavailable from BP Solvay Polyethylene North America, Houston, TX. Samplewas cut from the bottle. ²PP/EVOH/PP/PP bottle is commercially availableas Heinz Ketchup from H. J. Heinz Company, Pittsburgh, PA. Sample wascut from the bottle.

In general, the data indicates that increasing the barrier filmthickness decreases permeability to the sterilant gas ethylene oxide.There appeared to be differences, however, among materials of the samechemical class. For example, films 5-10 show significant permeabilitydifferences even though they belong to the same general chemical class.This may be related to the thickness of the primary barrier layer(fluorinated thermoplastic layer) and/or the crystallinity of theprimary barrier layer and/or other layers in the construction. Ingeneral, film constructions 7, 11, 17, 19, and 21-24 performed the bestwith permeability values of less than or equal to 0.011mg/ETO/hr/cm²/micron. It is also apparent that very thick HDPE (>2000micron) had relatively low permeability to ethylene oxide.

Example 2

The contents of twelve pouches constructed from twelve commerciallyavailable thermoplastic films of varying thickness were analyzed forETO, ECH, and EG using the Gaseous Ethylene Oxide Residuals Testdescribed in Test Protocols.

The description of the films is shown in Table 1a and the thickness ofthe films and results of the test are shown in Table 2.

TABLE 2 Thickness of Film, Volume of Water in Pouch, and ResidualsThickness Volume Residuals Film mils of Water ETO ECH EG No. (microns)(ml) (ppm) (ppm) (ppm) 20 3.00 (76.20) 45 20  ND¹ ND 12  5.00 (127.00)30 ND ND ND 9 1.00 (25.40) 57 ND ND ND 6 2.00 (50.80) 50 15 ND ND 253.00 (76.20) 40  1 ND ND 26  3.95 (100.33) 40 34 ND ND 27 2.40 (60.96)40 ND ND ND 28 4.00 (101.6) 40 ND ND ND 16 2.60 (66.04) 15  7 ND ND 291.00 (25.40) 15  4 ND ND 3 1.00 (25.40) 25  5 ND ND 4 1.00 (25.40) 25  9ND ND ¹ND means not detected. The test limit of detection is 1 part permillion.

Material selection was based on finding a film with very low ornon-detectable levels of ETO, ECH, or EG. The Gaseous ETO PermeabilityTest and the Gaseous ETO Residuals Test were found to correlate verywell over a range of permeabilities from 0 to 0.93 ml of ETO/hr/cm².Therefore, the simpler Gaseous ETO Residuals Test was used to qualifymaterials.

Example 3

Eleven coextruded trilaminated tubes (made by Teel Plastics Company,Baraboo, Wis.), which were sealed on one end, were filled with a givenvolume of water. The tubes had an outside diameter of 19 mm and were16.8 cm in length. A solid plastic plug milled from HDPE was glued intothe unsealed end with SCOTCH Weld DP 100 adhesive (commerciallyavailable from 3M). The filled tubes were sterilized in 3M STERIVAC 4XL100% ETO Sterilization Cycle for 4.2 hours at 37° C. and aerated for 2.2hours. The water was removed from the tubes and analyzed as describedfor Example 2. The tube chemical description, thickness, size andresults of analysis of a given volume of ETO Sterilized water arereported in Table 3.

In addition, two one layer HDPE tube samples which were obtained fromNorden Pac International, Kalmar, Sweden and two plastic ampoules (4inches (10.2 cm) in length and with an inner diameter of 0.74 inches(1.88 cm) with wall thicknesses as indicated in Table 3 were milled fromHDPE. The tubes and ampoules were filled with water, sterilized, and thewater was analyzed in a manner similar to the trilaminate tubes.

The results are also shown in Table 3

TABLE 3 Coextruded Tube Description and Results of Analysis of ETOSterilized Water Vol. of Residuals Tube Thickness Water ETO ECH EG No.Chemical Description (microns) (ml) (ppm) (ppm) (ppm) 1 HDPE³/CXA⁴/PET¹533.4/50.8/76.2 45 1 ND⁵ ND 2 HDPE/CXA/PET¹ 482.6/50.8/127.0 45 1 ND ND3 HDPE/CXA/PET¹ 304.8/50.8/177.8 45 1 ND ND 4 HDPE/CXA/PET¹254.0/50.8/228.6 45 1 ND ND 5 HDPE/CXA/PET² 533.4/50.8/76.2 45 63 1 2 6HDPE/CXA/PET² 482.6/50.8/127.0 45 ND ND ND 7 HDPE/CXA/PET²304.8/50.8/177.8 45 ND ND ND 8 HDPE/CXA/PET² 254.0/50.8/228.6 45 ND NDND 9 HDPE/Admer⁵/PET² 203.2/50.8/152.4 40 ND ND ND 10 HDPE/Admer/PET²254.0/50.8/152.4 40 ND ND ND 11 HDPE/Admer/PET² 304.8/50.8/152.4 40 NDND ND 12 HDPE⁷ 432.0 40 301 ND ND 13 HDPE⁷ 432.0 40 317 ND ND 14 HDPEAmpoule 2540.0 40 0.45 ND ND 15 HDPE Ampoule 3175.0 40 ND ND ND ¹PET iscommercially available from Eastman Chemical Co., Kingsport, TN. ²PET iscommercially available as DMT Clear Polyester from 3M, St. Paul, MN.³HDPE is commercially available as Polyethylene HHM 5202 from PhillipsMarlex, Houston, TX. ⁴CXA (Co-Extruded Adhesive) is commerciallyavailable as BYNEL 2169 anhydride-modified ethylene acrylate from E.I.du Pont deNemours and Company, Wilmington, DE. ⁵Admer is commerciallyavailable as ADMER AT1614A Adhesive from Mitsui Chemicals America, Inc.,Purchase, NY. ⁶ND means not detected. The test limit is 1 part permillion. ⁷HDPE tubes obtained from Norden Pac International, Kalmar,Sweden.

These examples demonstrate that constructions made from PET and HDPEprovide an excellent barrier to ETO. These constructions are alsotranslucent or transparent and are relatively thin and relatively lowcost to manufacture. The relatively thin polyethylene bottles (17-mil(432 microns)) had high levels (exceeding 300 ppm) of ethylene oxide.The HDPE ampoules having wall thicknesses of greater than 2500 microns,however, proved to be excellent barriers to the chemical sterilantethylene oxide. Note that this is consistent with the results of Example1, which showed that relatively thick HDPE was an effective barrier toethylene oxide.

Example 4 Ceramic Barriers

Several CERAMIS tubes were obtained from CCL Container a division of CCLInd., Don Mills, Ontario, Canada. The tubes had an internal diameter of0.88 in (2.2 cm) and a length (measured from the base of the neck to theend of the tube) of 4.52 in (11.48 cm) and were made from a laminateconstructed from the layers described in Table 4a.

TABLE 4a Description Layers and Thickness of Laminated Tube ConstructionLayer Thickness Number Description (microns) 1 Co extruded polyethylenefilm (tube interior) 150 2 Lacquer laminate 4 3 PET SiOx (Ceramis ™) 124 Lacquer laminate 4 5 Co extruded polyethylene films (tube exterior) 11On one end of the tube was a neck. Two neck designs were evaluated: 1) anasal tip with thread and 2) a larger opening with a #16 neck (threadedtip with an internal opening diameter of 0.313 in (0.795 cm) and anexternal thread diameter of 0.469 in (1.19 cm)). A foil laminate barrierfilm was thermally welded to the end of the neck of some tubes while amatching threaded cap was placed over the end of some other tubes.

Then the tubes were filled with approximately 26 ml of water through theend opposite the neck and thermally sealed using a bar heat sealer. TheCERAMIS tubes were all transparent allowing visualization of the fluidlevel.

The tubes were sterilized in a 3M STERIVAC 4XL Ethylene Oxide sterilizerusing canister 4-134 and a 37° C. cycle. The chamber of the sterilizerhad a volume of 115 liters. Ethylene oxide (127 g) was delivered by the4-134 canister yielding an ETO dose of 1104 mg/l. The tubes were removedin less than one hour after cycle completion (very little aeration time)and packed in dry ice until tested.

The tubes were tested for levels of ethylene oxide (ETO), ethylenechlorohydrins (ECH) and ethylene glycol (EG). Samples were testedaccording to ANSI/AAMPISO 10993-7 Biological Evaluation of MedicalDevices—Part 7: Ethylene oxide sterilization and ANSI/AAMI ST30:Determining Residual Ethylene Chlorohydrins and Ethylene Glycol inMedical Devices by Biotest Laboratories, Inc. Minneapolis, Minn. Foillaminate tubes were also obtained from CCL having a #16 tip and a foilseal for comparative purposes. Control tubes, which were filled withwater, but not sterilized were also tested to confirm the absence ofETO, ECH and EG.

The results of the test are shown in Table 4b.

TABLE 4b Residuals in Tubes Ethylene Ethylene Ethylene oxidechlorohydrins glycol Tube Description (ppm) (ppm) (ppm) Nasal Tip-Noseal 10  ND¹ ND with cap 9 ND ND 9 ND ND 10 ND ND 10 ND ND 7 ND ND 7 NDND 6 ND ND 12 ND ND 13 ND ND Mean 9.3 ND ND #16 neck w/ 6 <1 <1 seal-nocap 7 <1 <1 6 <1 <1 6 <1 <1 7 <1 <1 Mean 6.4 <1 <1 CCL CERAMIS 4 <1 <1#16 with foil seal 3 <1 <1 and cap 3 <1 <1 4 <1 <1 4 <1 <1 4 <1 <1 Mean3.6 <1 <1 CCL Foil Tubes 3 <1 <1 3 <1 <1 3 <1 <1 3 <1 <1 3 <1 <1 Mean 3<1 <1 Control <1 <1 <1 <1 <1 <1 <1 <1 <1 Mean <1 <1 <1 ¹ND means notdetectable. The test limit was 1 part per million.

The results indicate that the CERAMIS laminate was an excellent barrierto ethylene oxide. A combination of the foil seal and the cap over theend of the tube appeared to provide the least intrusion of ethyleneoxide into the tube and a level comparable to a foil tube.

Example 5

Seven sponges, which were either commercially available or available aspart of a dispenser, were evaluated for apparent surface energy usingthe Apparent Surface Energy Test Method described in the Test Protocols.

Table 5a contains a description of the sponges. Table 5b contains theApparent Surface Energy of the Sponges.

TABLE 5a Description of the Sponges Sponge Trade Name/ No. Generic NameDescription Source, Address 1 Illbruck Felted version of Foam #2Illbruck Inc., Sponge compressed 2.5:1. Minneapolis, MN 2 Illbruck P90Zreticulated, open pore, Illbruck Inc. Sponge flexible, polyester typepolyurethane sponge; pore size = 80-100 ppi; density = 1.9 lb/ft³;compressive force = 0.25 psi @ 25% compression and 0.45psi at 65%compression. 3 Wilsorb Flexible open cell, polyester, Illbruck Inc.polyurethane polyurethane foam; sponge Density = 1.8 lb/ft³ (ASTM 3574)Compressive force = 0.56 psi @ 25% compression or 0.81 psi @ 65%compression; Pore size = 85 ppi 4 QFC-90SW Reticulated open cell QFCIndustries, Sponge Stick polyurethane Arlington, TX 5 Allegiance- FoamAllegiance, Cat. No. 4463 McGaw Park, IL 6 Previal FX-Cat. AllegianceNo. 4vail-FX 7 Pharmaseal Reticulated open cell Baxter Scrub Carepolyurethane sponge Heatlhcare Surgical Scrub Corp., Pharmseal Brushsponge, Div., Valencia, Cat. No. 4454A CA

TABLE 5b Apparent Surface Tension of Sponges Sponge Apparent SurfaceTension Number (dynes/cm at 23° C.) 1 33 2 30 3 Greater than 72 (wettedby deionized water) 4 30 5 30 6 Less than 28 (Fluid 1 did not wet) 7 33

The commercially available sponges used to disinfect the skin of apatient or the hands of clinicians tested (Sponge No. 1, 2, 4, 5, 6, and7) were found to have apparent surface energies of less than or equal to33 dynes/cm when tested at 23° C. The hydrophilic sponge (Sponge No. 3)was found to have an apparent surface energy greater than that of water(72 dynes/cm) and much greater that 33 dynes/cm when tested at 23° C.

Example 6

The hydrophilic sponge (Sponge No. 3 in Example 5) and the hydrophobicsponge (Sponge No. 4) were used to apply antiseptic formulations A and Bin Table 6a to the skin of human volunteers using the Human SkinAntimicrobial Activity described in the Test Protocols.

TABLE 6a Antiseptic Formulations Formulation A B Component CAS No.(weight percent) (weight percent) Acrylate polymer¹ 5.00 5.00Povidone-iodine USP² 7.50 7.50 Lactic acid³   79-33-4 5.00 5.00 Malicacid⁴  617-48-1 2.00 2.00 Brij 700⁵  9005-00-9 1.40 0.75 MACKAM 50-SB⁶68139-30-0 0.00 1.25 CRODAPHOS SG⁷ 73361-29-2 1.00 0.00 AMMONYX LMDO⁸Confidential 0.75 0.00 Water 77.35 78.50 pH 3.5-4 3.5-4 ¹Amine oxidepolymer (stearylmethacrylate (10%)/iotabutyl methacrylate (20%)/amineoxide of dimethylaminomethylmethacrylate (50%)/methylmethacrylate(20%))commercially available from 3M, St. Paul, MN. ²Povidone-iodine USP iscommercially available from BASF Corporation, Mt. Olive, NJ. ³Lacticacid, High Pure 88, USP is commercially available from Purac America,Lincolnshire, IL. ⁴Malic acid, DL, is commercially available fromUniversal Preserv-a-Chem, Edison, NJ. ⁵BRIJ 700 steareth-10 iscommercially available from ICI, Wilmington, DE. ⁶MACKAM 50-SBcocamidopropylhydroxysultaine is commercially available from McIntyreGroup Ltd., Unversity Park, IL. ⁷CRODAPHOS SG PPG-5-Ceteth-10 phosphateis commercially available from Croda, Inc., Parsippany, NJ. ⁸AMMONYXLMDO lauramidopropyldimethylamine oxide is commercially available fromStepan, Northfield, IL,

Raw data was converted to Log_(ic)) Colony Forming Unit (CFU)/cm². Thelog reduction was calculated for each of the prep formulations bysubtracting the post-prepping log counts from the average of duplicatebaseline log counts. Means and standard deviations of log counts and logreductions were calculated. Since the study was a randomized blockdesign each subject received each treatment. The primary comparisons ofinterest were the hydrophilic Sponge No. 3 versus the hydrophobic SpongeNo. 4 on a stick.

Table 6b shows the resulting log reductions.

TABLE 6b Means and Standard Deviations of Log Reductions for AntisepticFormulations, A and B on Sponge No. 3 and Sponge No. 4 Subjects withSubjects Base Base line line counts counts equal to less than 2.5 ormore 2.5 (log All Subjects Sponge (log reduction) reduction) (logreduction) Prep No. N¹ Mean Std² N Mean Std N Mean Std A 4 4 0.8 1.8 41.9 0.5 8 1.3 1.4 A 3 4 2.5 1.1 4 2.2 0.2 8 2.3 0.7 B 4 4 0.6 1.4 4 1.90.9 8 1.2 1.3 B 3 4 2.3 1.2 4 2.1 0.2 8 2.2 0.8 Control Gauze 4 2.5 1.04 1.7 1.2 8 2.1 1.1 ¹N means number of subjects ²Std means standarddeviation.

The results surprisingly indicate that for both antiseptic formulations,A and B, hydrophilic Sponge No. 3 resulted in significantly higher logreduction compared to hydrophobic Sponge No. 4 (probability <0.03).

The preceding specific embodiments are illustrative of the practice ofthe invention. This invention may be suitably practiced in the absenceof any element or item not specifically described in this document. Thecomplete disclosures of all patents, patent applications, andpublications are incorporated into this document by reference as ifindividually incorporated in total.

Various modifications and alterations of this invention will becomeapparent to those skilled in the art without departing from the scope ofthis invention, and it should be understood that this invention is notto be unduly limited to illustrative embodiments set forth herein, butis to be controlled by the limitations set forth in the claims and anyequivalents to those limitations.

1-15. (canceled)
 16. A skin antiseptic composition dispenser comprising:a container defining an interior volume, skin antiseptic compositionlocated within the interior volume of the container; and dispensingmeans for dispensing the skin antiseptic composition; wherein thecontainer comprises a first layer impermeable to liquid and vapor phasesof the skin antiseptic composition having an interior surface adjacentthe skin antiseptic composition; a barrier layer that is substantiallyimpermeable to gaseous ethylene oxide, and an adhesive adhering thebarrier layer to at least a portion of an exterior surface of the firstlayer; wherein the first layer and the barrier layer each independentlycomprise one or more polymeric walls free of metallic foil layers. 17.The dispenser according to claim 16, wherein the barrier layer coversless than 100% of the first layer.
 18. The dispenser according to claim17, wherein the barrier layer covers at least 60% of the first layer.19. The dispenser of claim 18, wherein the adhesive layer comprises apressure sensitive adhesive.
 20. The dispenser of claim 19, wherein thepressure sensitive adhesive comprises and acrylic based adhesive. 21.The dispenser of claim 19, wherein the pressure sensitive adhesivecomprises an elastomer selected from the group consisting of naturalrubber, and synthetic rubbers comprising polymers and/or copolymers ofstyrene, butadiene, acrylonitrile, isoprene and isobutylene.
 22. Thedispenser according to claim 18, wherein the skin antiseptic compositioncomprises an agent selected from the group consisting of iodine, aniodine complex, chlorhexidine, triclosan, octenidine and combinationsthereof.
 23. The dispenser of claim 22, wherein the iodine complexcomprises an iodophor.
 24. The dispenser of claim 22, wherein thechlorhexidine comprises a chlorhexidine salt.
 25. The dispenser of claim24, wherein the chlorhexidine salt is selected from the group consistingof chlorhexidine digluconate and chlorhexidine diacetate.
 26. Thedispenser according to claim 18, wherein the first layer and the barrierlayer are flexible.
 27. The dispenser according to claim 18, wherein thecontainer is cylindrical.